Today adjuvants are used to enhance the immunogenicity of antigens which are not replicating i.e. in so-called killed or inactivated vaccines. Although, many vaccines contain several kinds of vaccine antigens in order to cover immune protection against several infectious diseases live and killed vaccine antigens are not mixed. One reason for that is that killed vaccines need adjuvant to enhance the efficacy of killed vaccines.
Live vaccines contain micro-organisms that replicate in the host i.e. the live attenuated vaccine antigens which are micro-organisms that are closely related to the pathogen i.e. the micro-organisms that cause disease. Thus, the host is producing most of the vaccine antigens when replicating vaccine antigens are used resulting in in vivo production of high doses of vaccine antigens in the host.
Moreover, the production of vaccine antigens in the host over a period of time contributes also to make the live vaccines effective, and even one administration of an efficient live vaccine often suffices to evoke long lasting immune protection. For certain pathogens there is no live properly attenuated micro-organism available to present them in a vaccine, either because the attenuation is not achieved, or that after the attenuation the micro-organism does not induce a potent immune protection.
There are both practical and economical reasons to give the vaccine antigens in one or as few administrations as possible, when there is a defined period for vaccination. Such a period is in the early childhood respectively new-born animals when a vaccine for protection against up to seven different infectious diseases are given in one injection. Another period is when a large number of animals are gathered in e.g. fattening units form different farms and regions. Still another such a period is before travel to exotic countries to induce immune protection against exotic infectious diseases, i.e. pathogens that are not present in the home country.
Most vaccines for dogs are used in puppies and the first vaccination is carried out just before or at the time for delivery to the new owner. There is a strong tendency, not to say desire, to avoid more than one primary administration of vaccine and limit the number of re-vaccinations. Most vaccines in dogs are live and killed vaccine antigens are avoided in multicomponent dog and cat vaccines, mainly due to the fact of the difficulty to combine live and killed vaccines. Thus a dog vaccine today is mostly a live multicomponent vaccine (and) composed to protect against up to seven different infectious diseases.
A frequently used killed vaccine for dog and cat is the rabies virus vaccine. Bordetella bronchiseptica (Bb) is also desired as a killed vaccine, since the live vaccine causes side effects. A killed Bb component vaccine (sub unit) would need adjuvant supplementation. These vaccines are single component vaccines. The killed Rabies virus vaccine requires adjuvant, and so far aluminium hydroxide is used, which adsorbs the micro-organisms and interferes thereby with their replication.
In cat, the feline leukemia virus is a killed vaccine (sub unit) based on gp70, being a surface protein of the virus. Also this vaccine antigen requires adjuvant. The present used adjuvant formulation is composed of free saponin (QS21) and Al(OH)3, a mixture that will lyse viral membranes and kill the virus. The AI(OH)3 component causes in rare cases fibrosarcoma, conceived to be caused by the depot effects of some adjuvants e.g., oil or Al(OH)3 (report from the Veterinary Products Committee Working Group on Feline and Canine Vaccination Department for Environment, Food & Rural Affairs (DEFRA) Publications Admail 6000 London SWIA2XX).
Thus, there is a desire to be able to use killed and live vaccines mixed in a common formulation and that they should be compatible with each other in the formulation. Further an adjuvant present in a vaccine formulation must not cause adverse side effects.
It has now surprisingly turned out that iscoms and iscom matrix particles can be used as adjuvants for killed vaccine antigens e.g. in a multi component vaccine without causing negative effects on the live replicating vaccine components. This is contrary to most (other) commonly used adjuvants that decrease the capacity of the live microorganisms to replicate.
Unexpectedly, the iscom/iscom-matrix adjuvant was not only harmless to the live components, it also enhanced the immune response against the live vaccine components.